tbuckley/cabot-search huggingface dataset:
Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2)
Authors: Sai-Hong Ignatius Ou, Makoto Nishio, Myung-Ju Ahn, Tony Mok, Fabrice Barlesi, Caicun Zhou, Enriqueta Felip, Filippo de Marinis, Sang-We Kim, Maurice Pérol, Geoffrey Liu, Maria Rita Migliorino, Dong-Wan Kim, Silvia Novello, Alessandra Bearz, Pilar Garrido, Julien Mazieres, Alessandro Morabito, Huamao M. Lin, Hui Yang, Huifeng Niu, Pingkuan Zhang, Edward S. Kim
Journal: Journal of Thoracic Oncology (2022)

<h2>Abstract</h2><h3>Introduction</h3> Brigatinib is a potent next-generation ALK tyrosine kinase inhibitor approved for treatment-naive and crizotinib-refractory advanced <i>ALK</i>-positive (<i>ALK+</i>) NSCLC. We evaluated brigatinib after other next-generation ALK tyrosine kinase inhibitors. <h3>Methods</h3> In this single-arm, phase 2, ALK in Lung Cancer Trial of brigAtinib-2 (NCT03535740), patients with advanced <i>ALK+</i> NSCLC whose disease progressed on alectinib or ceritinib received brigatinib 180 mg once daily (after 7-d 90-mg lead-in). Primary end point was independent review committee (IRC)-assessed overall response rate (ORR). Circulating tumor DNA (ctDNA) was analyzed. <h3>Results</h3> Among 103 patients (data cutoff: September 30, 2020; median follow-up [range]: 10.8 [0.5–17.7] mo), confirmed IRC-ORR was 26.2% (95% confidence interval [CI]: 18.0–35.8), median duration of response, 6.3 months (95% CI: 5.6–not reached), and median progression-free survival (mPFS), 3.8 months (95% CI: 3.5–5.8). mPFS was 1.9 months (95% CI: 1.8–3.7) in patients with ctDNA-detectable baseline <i>ALK</i> fusion (n = 64). Among 86 patients who progressed on alectinib, IRC-ORR was 29.1% (95% CI: 19.8–39.9); mPFS was 3.8 months (95% CI: 1.9–5.4). Resistance mutations were present in 33.3% (26 of 78) of baseline ctDNA; 54% (14 of 26) of mutations were G1202R; 52% (33 of 64) of patients with detectable <i>ALK</i> fusion had <i>EML4-ALK</i> variant 3. Most common all-grade treatment-related adverse events were increased creatine phosphokinase (32%) and diarrhea (27%). The mean dose intensity of brigatinib (180 mg once daily) was 85.9%. <h3>Conclusions</h3> In ALK in Lung Cancer Trial of brigAtinib-2, brigatinib was found to have a limited activity in patients with <i>ALK</i>+ NSCLC post-ceritinib or post-alectinib therapy. mPFS was longer with brigatinib in patients without baseline detectable plasma <i>ALK</i> fusion.
Therapy with voretigene neparvovec. How to measure success?
Authors: Krunoslav Stingl, Melanie Kempf, Ronja Jung, Friederike Kortüm, Giulia Righetti, Milda Reith, Spyridon Dimopoulos, Saskia Ott, Susanne Kohl, Katarina Stingl
Journal: Progress in Retinal and Eye Research (2022)

Retinal gene supplementation therapy such as the first approved one, voretigene neparvovec, delivers a functioning copy of the missing gene enabling the protein transcription in retinal cells and restore visual functions. After gene supplementation for the genetic defect, a complex network of functional regeneration is the consequence, whereas the extent is very individualized. Diagnostic and functional testings that have been used routinely by ophthalmologists so far to define the correct diagnosis, cannot be applied in the new context of defining small, sometimes subtle changes in visual functions. New view on retinal diagnostics is needed to understand this processes that define safety and efficacy of the treatment. Not only does vision have many aspects that must be addressed by specific evaluations and imaging techniques, but objective readouts of local retinal function for rods and cones separately have been an unmet need until recently. A reliable test-retest variability is necessary in rare diseases such as inherited retinal dystrophies, because statistics are often not applicable due to a low number of participants. Methods for a reliable individual evaluation of the therapy success are needed. In this manuscript we present an elaboration on retinal diagnostics combining psychophysics (eg. full-field stimulus threshold or dark adapted perimetry) as well as objective measures for local retinal function (eg. photopic and scotopic chromatic pupil campimetry) and retinal imaging for a meaningful workflow to apply in evaluation of the individual success in patients receiving gene therapy for photoreceptor diseases.
Statistics in Oncology
Authors: Sean Devlin, Alexia Iasonos
Journal: Journal of Clinical Oncology (2022)

Article Tools OVERVIEWS Special Series: Statistics in Oncology Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.22.01457 Journal of Clinical Oncology - published online before print September 12, 2022 PMID: 36095293 Statistics in Oncology Sean Devlin , PhD1xSean DevlinSearch for articles by this author and Alexia Iasonos , PhD1xAlexia IasonosSearch for articles by this author Show More 1Memorial Sloan Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.22.01457 First Page Full Text PDF Figures and Tables © 2022 by American Society of Clinical OncologyAUTHOR CONTRIBUTIONSConception and design: All authorsCollection and assembly of data: All authorsData analysis and interpretation: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTStatistics in OncologyThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Sean DevlinThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Miltenyi BiotecAlexia IasonosThis author is a Deputy Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Stock and Other Ownership Interests: Bristol Myers Squibb/SanofiConsulting or Advisory Role: Intelligencia, Mirati TherapeuticsNo other potential conflicts of interest were reported.
Association of Sociodemographic Characteristics With Survival Among Patients With Urachal Cancer in California From 1988 to 2019
Authors: David J. Benjamin, Anshu Shrestha, Dimitra Fellman, Rosemary D. Cress, Arash Rezazadeh Kalebasty
Journal: JAMA Oncology (2022)

This cohort study evaluates the sociodemographic characteristics of patients with urachal cancer, cancer treatments, and the association of patient characteristics with overall survival.
Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial
Authors: Sungjune Kim, Evan Wuthrick, Dukagjin Blakaj, Zeynep Eroglu, Claire Verschraegen, Ram Thapa, Matthew Mills, Khaled Dibs, Casey Liveringhouse, Jeffery Russell, Jimmy J Caudell, Ahmad Tarhini, Joseph Markowitz, Kari Kendra, Richard Wu, Dung-Tsa Chen, Anders Berglund, Lauren Michael, Mia Aoki, Min-Hsuan Wang, Imene Hamaidi, Pingyan Cheng, Janis de la Iglesia, Robbert J Slebos, Christine H Chung, Todd C Knepper, Carlos M Moran-Segura, Jonathan V Nguyen, Bradford A Perez, Trevor Rose, Louis Harrison, Jane L Messina, Vernon K Sondak, Kenneth Y Tsai, Nikhil I Khushalani, Andrew S Brohl
Journal: The Lancet (2022)
Modern Methods of Treatment.
Journal: JAMA (1924)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
GRADUATE MEDICAL EDUCATION
Journal: JAMA (1965)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Manual of Diseases of the Nose, Throat, and Ear
Journal: JAMA (1934)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord Injury
Authors: Michael B. Bracken
Journal: JAMA (1997)

<h3>Objective.</h3> —To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. <h3>Design.</h3> —Double-blind, randomized clinical trial. <h3>Setting.</h3> —Sixteen acute spinal cord injury centers in North America. <h3>Patients.</h3> —A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. <h3>Intervention.</h3> —All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. <h3>Main Outcome Measures.</h3> —Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. <h3>Results.</h3> —Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (<i>P</i>=.09) and 6 months (<i>P</i>=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (<i>P</i>=.04) and 6 months (<i>P</i>=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (<i>P</i>=.03) at 6 months, to show more improvement in 6-month FIM (<i>P</i>=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (<i>P</i>=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. <h3>Conclusions.</h3> —Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.
Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans.
Authors: M J McNeely, E J Boyko, D S Weigle, J B Shofer, S D Chessler, D L Leonnetti, W Y Fujimoto
Journal: Diabetes Care (1999)

OBJECTIVE: Plasma leptin levels correlate strongly with increased total adipose tissue, a known risk factor for type 2 diabetes, yet the role of leptin in the etiology of diabetes remains unclear. We sought to determine whether leptin is a risk factor for development of diabetes in Japanese Americans. RESEARCH DESIGN AND METHODS: We compared baseline leptin levels in 370 nondiabetic Japanese Americans who remained nondiabetic for 5-6 years of follow-up with those of 40 nondiabetic Japanese Americans who developed diabetes during follow-up. All participants had computed tomography measurements of baseline subcutaneous chest, abdomen, thigh, and intra-abdominal fat, with total fat defined as the sum of all these measurements. RESULTS: The mean age was 51.7 +/- 11.7 years for men and 51.9 +/- 12.0 years for women. The 23 men who developed diabetes had significantly higher leptin levels than the 212 men who remained nondiabetic (P &amp;lt; 0.01). Among men, baseline leptin levels predicted diabetes risk independent of baseline total fat, insulin, insulin resistance, glucose, or age in separate multiple logistic regression models (relative risk adjusted for baseline total fat = 1.80 per SD increase [2.7 ng/ml], 95% CI 1.02-3.17). This association was particularly strong among men in the top decile for intra-abdominal fat. In contrast, the 17 women who developed diabetes had leptin levels similar to those of the 158 women who remained nondiabetic (P = 0.31). CONCLUSIONS: Among Japanese Americans, increased baseline leptin levels are associated with increased risk of developing diabetes in men but not in women.
Unpackaging cultural variability in behavioral phenotypes
Authors: Ronald Fischer
Journal: Behavioral and Brain Sciences (2022)

Abstract We need better understanding of functional differences of behavioral phenotypes across cultures because cultural evolution (e.g., temporal changes in innovation within populations) is less important than culturally molded phenotypes (e.g., differences across populations) for understanding gene effects. Furthermore, changes in one behavioral domain likely have complex downstream effects in other domains, requiring careful parsing of phenotypic variability and functions.
Evolving the blank slate
Authors: Timothy C. Bates
Journal: Behavioral and Brain Sciences (2022)

We support Uchiyama et al. in the value of genetics, sample diversification, and context measurement. Against the example of vitamins, we highlight the intransigence of many phenotypes. We caution that while culture can mask genetic differences, the dependence of behaviour on genetics is reinvented and unmasked by novel challenges across generations.
The dubious precision and utility of heritability estimates
Authors: Steven J. Heine, Ilan Dar-Nimrod
Journal: Behavioral and Brain Sciences (2022)

Uchiyama et al. question heritability estimates in a convincing manner. We offer additional arguments to further bolster their claims, highlighting methodological issues in heritability coefficients' derivation, their misuse in various contexts, and their potential contributions to exacerbating common erroneous intuitions that have been shown to lead to deleterious social phenomena. We conclude that science should move away from using them.
Heritability is a poor, if not unhelpful, measure of complex human behavioral processes
Authors: Agustín Fuentes, Kevin Bird
Journal: Behavioral and Brain Sciences (2022)

Abstract Heritability is not a measure of the relative contribution of nature vis-à-vis nurture, nor is it the phenotypic variance explained by or because of genetic variance. Heritability is a correlative value. The evolutionary and developmental processes associated with human culture challenge the use of “heritability” for understanding human behavior.
The evolutionary dance between culture, genes, and everything in between
Authors: Abdel Abdellaoui
Journal: Behavioral and Brain Sciences (2022)

Uchiyama et al. describe how a more complete measurement of the dynamic nature of culture could help us unmask the true richness of genetic effects on behaviour. I underscore this notion here by reflecting on the role that the dynamic relationship between culture and DNA has played in our evolutionary history and will play in our evolutionary future.
Culture and causal inference: The impact of cultural differences on the generalisability of findings from Mendelian randomisation studies
Authors: Amy Campbell, Marcus R. Munafò, Hannah M. Sallis, Rebecca M. Pearson, Daniel Smith
Journal: Behavioral and Brain Sciences (2022)

Abstract Cultural effects can influence the results of causal genetic analyses, such as Mendelian randomisation, but the potential influences of culture on genotype–phenotype associations are not currently well understood. Different genetic variants could be associated with different phenotypes in different populations, or culture could confound or influence the direction of the association between genotypes and phenotypes in different populations.
Cultural evolution: The third component of mental illness heritability
Authors: Davide Amato
Journal: Behavioral and Brain Sciences (2022)

Abstract Uchiyama et al. provide a theoretical framework to explain the gap between reported gene–environment interactions and real-life epidemiological statistics. Through cultural evolution, informed behavioral approaches mitigate the impact of environmental risk on disease onset. Similarly, here we propose that fostering certain behavioral traits, transmitted culturally or through access to scientific knowledge, could confer resilience to mental illnesses such as schizophrenia.
From the trajectory of heritability to the heritability of trajectories
Authors: Rogier A Kievit, Jessica A Logan, Sara A Hart
Journal: Behavioral and Brain Sciences (2022)

Abstract Although compelling and insightful, the proposal by Uchiyama et al. largely neglects within-person change over time, arguably the central topic of interest within their framework. Longitudinal behavioural genetics modelling suggests that the heritability of trajectories is low, in contrast to high and increasing cross-sectional heritability across development. Better understanding of the mechanisms of trajectories remains a crucial outstanding challenge.
A call to prioritise prevention: Action is needed to reduce the risk of zoonotic disease emergence
Authors: Sarah Shanks, May CI van Schalkwyk, Andrew A. Cunningham
Journal: The Lancet Regional Health - Europe (2022)

Anthropogenic changes to the environment are facilitating the spread of animal pathogens into human populations. A global focus on detecting and containing emerging infectious diseases has deflected from the need for upstream prevention measures to reduce the risk of pathogen emergence. The drivers of infectious disease emergence have predominantly been considered as environmental and conservation issues and not as risks to human health. There is an opportunity for the UK to take a leadership position on this complex issue. This will require the establishment and maintenance of effective governance and policy mandates. Novel ways of policymaking are needed urgently to achieve three key aims: coordination and collaboration across sectors and government departments, the inclusion of diverse expertise, and the prioritisation of measures directed at prevention.
The many geographical layers of culture
Authors: Friedrich M. Götz, Tobias Ebert, Peter J. Rentfrow
Journal: Behavioral and Brain Sciences (2022)

Uchiyama et al. present a dual inheritance framework for conceptualizing how behavioural genetics and cultural evolution interact and affect heritability. We posit that to achieve a holistic and nuanced representation of the cultural environment and evolution against which genetic effects should be evaluated, it is imperative to consider the multiple geographic cultural layers impacting individuals and genetic heritability.
Cultural dynamics add multiple layers of complexity to behavioural genetics
Authors: Laurel Fogarty, Nicole Creanza
Journal: Behavioral and Brain Sciences (2022)

As emphasized in early cultural evolutionary theory, understanding heritability of human traits – especially, behavioural traits – is difficult. The target article describes important ways that culture can enhance, or obscure, signatures of heritability in genetic studies. Here, we discuss the utility of calculating heritability for behavioural traits influenced by cultural evolution and point to conceptual and technical complications to consider in future models.
Cultural evolutionary theory is not enough: Ambiguous culture, neglect of structure, and the absence of theory in behavior genetics
Authors: Callie H. Burt
Journal: Behavioral and Brain Sciences (2022)

Abstract Uchiyama et al. propose a unified model linking cultural evolutionary theory to behavior genetics (BG) to enhance generalizability, enrich explanation, and predict how social factors shape heritability estimates. A consideration of culture evolution is beneficial but insufficient for purpose. I submit that their proposed model is underdeveloped and their emphasis on heritability estimates misguided. I discuss their ambiguous conception of culture, neglect of social structure, and the lack of a general theory in BG.